The results of this study indicate that the advantage normal elderly women have over men in learning and recalling verbal episodic memory disappears or reverses in AD. Control women outperformed Control men in every measure of the Logical Memory subtest (). This was true for both Stories A and B and despite a time delay between the immediate recall and the delayed recall. Additionally, Control women had a higher rate of learning between the first and second immediate recalls of Story B (). Men and women appeared to forget story details at a similar rate during a time delay filled with other activity (as depicted by loss of accuracy in detail recollection between the second immediate recall of Story B and the delayed recall in ).
In the AD group, however, it is men who outperform women in tasks of verbal episodic memory. On average, AD men scored higher than women on every aspect of the Logical Memory (across both stories and across the time delay). Clearly the better performance in women over men that was striking and statistically significant in normal elderly Controls has disappeared or reversed in AD, a conclusion supported by statistically significant Group × Gender interactions ( and ). This finding is most apparent in where the solid lines representing immediate recalls, as well as the dashed lines for delayed recalls, cross for each gender when moving from Control to AD. Control women scored higher on average than Control men for both stories and both immediate and delayed recalls, and this trend was reversed in AD (such that AD women scored lower on average than AD men). Additionally, the improved rate of learning seen in Control women disappears in AD women, though the rate of forgetting between AD men and women appears to be the same ().
These findings are consistent with results reported by others that gender differences are present in AD and relevant to the study of the disease (Buckwalter, Sobel, Dunn, Diz, & Henderson, 1993
; McPherson, et al., 1999
). Significant gender effects may be easier to detect when AD subjects are more advanced in the disease (Beinhoff, et al., 2008
). In order to focus on very mild AD, our inclusion criteria required a higher score on the MMSE (≥22 in this study and in Beinhoff et al. versus ≥15 in McPherson et al.’s study). It is possible that the gender differences favoring men become more pronounced as AD progresses, as others have suggested (Ripich, et al., 1995
). In some studies of gender differences in AD, their samples of AD subjects were moderately to greatly impaired at the time of analysis as indicated by low mean MMSE scores (Buckwalter et al., 1996
; Buckwalter, et al., 1993
) and significant differences on the MMSE between AD men and women were found (Buckwalter, et al., 1993
). We had no such gender difference on the MMSE in our AD group ().
There have been some inconsistencies in the literature concerning whether or not AD women perform significantly worse than AD men on semantic tasks (Beinhoff, et al., 2008
). We believe it is important to consider the performance of normal elderly when assessing gender differences in AD. For instance, the drop in performance from Control to AD for the five measures we studied in the LM was approximately constant for women (M
= −10.8, SD
= 1.9, N
= 5) and for men (M
= −6.7, SD
= 1.4, N
= 5). These drops were statistically greater for women than for men (t
(8) = 3.91, p = .005); on average they were 1.6 times greater for women. Moreover, these are sizeable drops considering the full range of scores is 0–25. In general, statistically significant differences between AD women and AD men may not appear on every measure because women have to fall so far from their normal control performance to be significantly below men as ADs. Therefore, where women and men start (normal cognition) is important in evaluating the gender difference related to AD.
The comparison of normal elderly to AD in terms of gender differences reveals two important findings. First, when other demographic variables (including age, education, handedness) are controlled, gender differences still impact performance on the LM in normal elderly and in an opposite direction in AD. Second, not only do normal, healthy older women outperform healthy older men, this advantage strikingly disappears in AD. This suggests that AD pathology may affect memory systems differently in women than in men (Cushman & Duffy, 2007
However, it has also been suggested that estrogen replacement therapy may provide protective effects on cognition and verbal memory in women (Henderson, Watt, & Buckwalter, 1996
; Kampen & Sherwin, 1994
; Korol & Manning, 2001
); see also Baum (Baum, 2005
). Because of a limited sample size of only three women in our subject pool actively taking hormone replacement therapy and limited knowledge of our subjects’ previous medications, we could not explore the effects of this treatment on cognitive performance. It is possible that our AD women perform poorly on the LM because by chance the vast majority of them did not receive hormone replacement therapy at the onset of menopause. It has been shown that women taking estrogen replacement therapy during menopause have a reduced risk of cognitive impairment and dementia later in life (Maki, 2006
; Tang et al., 1996
; Yaffe, Sawaya, Lieberburg, & Grady, 1998
; Zandi et al., 2002
), and many of our Control women have perhaps benefited from this effect. Though the cause of improved verbal memory in normal elderly women and diminished verbal memory in AD women in this study cannot be definitely stated, the fact that women with AD tended to exhibit poorer verbal memory skills than AD men must be considered when using the LM as a diagnostic tool.
It is also possible that AD affects verbal IQ differently in women, and this IQ gender difference could have influenced our LM results. If this were so, we would expect significant gender effects on the AMNART estimated verbal IQ similar to our main LM interaction. We found no significant gender effect or significant group by gender interaction in our analysis of the AMNART (see Methods), so we cannot infer that the interaction we report on the LM is due to overall lower estimated verbal IQ in women.
Effect of Gender Differences on AD Diagnosis
Our findings suggest an interesting and possibly diagnostically important fact about the Logical Memory test. This test has proven to be particularly useful in differentiating normal elderly from AD with high sensitivity and specificity (Chapman, et al., 2010
; Storandt & Hill, 1989
). The drop in performance from healthy cognition to AD is much larger in women than in men. For immediate recall, women drop on average over both stories 9.6 recall items whereas men drop only 5.7. Similarly, for delayed recall, women drop on average 12.5 and men drop only 8.1. Due to this larger drop in performance in women, it is possible the LM may more reliably detect AD in women. To examine this, we applied discriminant analysis to the LM measures of men and women separately to classify each as a member of the AD or Control group. We found that the LM was capable of diagnosing AD in women with 100% accuracy, and this was 22% more accurate than our discrimination results with men. In addition, the posterior probabilities were significantly higher for women () than for men, which suggests that these correct diagnoses for women were made with extremely high confidence (higher than the classifications for many of the men). This concept of the LM providing greater diagnostic power for women than men requires further study, but such a gender difference in diagnostic specificity has been reported for other measures of the WMS-III (Heaton, Taylor, & Manly, 2003
). Taking gender into account when assessing cognitive decline with the LM may increase its power in early detection of AD.
We are unaware of any published, validated normative data for the LM that take gender into account. However, standardizing the data to account for gender differences produces essentially the same discriminant results. We included every normal elderly subject we had available to produce LM normative data separately for men and women and standardized each gender accordingly (there were an additional 49 Control women and 41 Control men, totaling 70 Control women and 62 Control men. These individuals were not included in the main analysis to maintain balance with the AD group). The normalized scores for the LM entered into discriminant analysis for women and men separately and achieved essentially the same results as the non-normalized data: 99% of the women and 87% of the men were correctly classified.
Although cognitively healthy women and men exhibited a statistically significant gender difference on the MMSE, the MMSE is not as capable of detecting AD in women as the LM. The MMSE has been shown to not be a powerful tool at detecting AD (Chapman, et al., 2010
; Costa et al., 1996
; Heun, Papassotiropoulos, & Jennssen, 1988
). Using the same subjects whose LM data is reported here, we found the MMSE could detect AD in women with 83% accuracy and in men with 74% accuracy. While the LM detected AD significantly better in women than in men, the MMSE did not show such a gender difference (Fisher’s Exact Test, χ2
= 42) = 1.13, p
= .29). In addition, the LM achieved significantly higher accuracy in detecting AD in women over what the MMSE achieved (Fisher’s Exact Test, χ2
= 42) = 7.63, p
= .001). The MMSE and LM did not perform significantly differently in diagnosing AD in men (Fisher’s Exact Test, χ2
= 42) = 2.79, p
= .10). The MMSE is not as useful a tool in detecting AD, and the gender effect that boosts the power the LM has in assessing women is not present.
Our LM results require further examination with the WMS-IV, though it seems likely that the gender effects would persist given the minor changes to the LM in the newer version of the test. Additionally, we chose to focus on early-stage AD as identification of those individuals in the earliest stage of the disease is increasingly important, as well as understanding the nascent cognitive changes associated with early symptoms. These gender differences should be studied both (1) in individuals with more advanced AD to better understand their relationship to the progression of the disease and (2) in individuals with Mild Cognitive Impairment and preclinical AD.